Our work has concentrated on the role of the c-src proto-oncogene in normal development and in tumorigenesis. Determination of mechanism and pattern of c-src activation. We have found that activation of the c-src proto-oncogene can be measured as a function of increased tyrosine protein kinase activity of the gene product, a 60 kd protein, pp60c-src. We have shown that while most normal tissues have low levels of kinase activity, all tumor and normal cells of neuroectodermal origin that express a neuronal phenotype have enhanced activity. Thus, neuroblastoma, pheochromocytoma, neuroepithelioma, medulloblastoma and normal brain and adrenal medulla have 20-100 times more pp60c-src protein kinase activity than do glioblastomas, fibroblasts, or non-neural normal tissue. Biochemical analysis has revealed that this is not secondary to elevated c-src mRNA or pp60c-src protein and thus is an increse in the specific activity of the enzyme. A new tyrosine phosphorylation of the aminoterminal portion of pp60c-src has been associated with activation of the neuroboastoma enzyme. This is the first example of post-transational activation of an oncogene.